Journal
JOURNAL OF CELL BIOLOGY
Volume 204, Issue 6, Pages 931-945Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201305148
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Funding
- INSERM
- CNRS
- Universite Paris-Diderot
- Institut Universitaire de France
- Ligue Contre le Cancer
- Institut National du Cancer
- Association pour la Recherche contre le Cancer (Griffuel Award to H. de The)
- Canceropole Ile de France, the European Research Council (STEMAPL advanced grant to H. de The)
- PACRI
- Saint Louis Institute
- French National Research Agency (ANR) as part of the Investissements d'Avenir program [ANR-11-PHUC-002]
- Fondation pour la Recherche Medicale
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The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization. Oxidized PML spherical meshes recruit UBC9, which enhances PML sumoylation, allow partner recruitment through SIM interactions, and ultimately enhance partner sumoylation. Intermolecular SUMO-SIM interactions then enforce partner sequestration within the NB inner core. Accordingly, oxidative stress enhances NB formation and global sumoylation in vivo. Some NB-associated sumoylated partners also become polyubiquitinated by RNF4, precipitating their proteasomal degradation. As several partners are protein-modifying enzymes, NBs could act as sensors that facilitate and confer oxidative stress sensitivity not only to sumoylation but also to other post-translational modifications, thereby explaining alterations of stress response upon PML or NB loss.
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